TNF

Overview

Tumor necrosis factor, commonly abbreviated TNF and often referred to as TNF-α in its soluble cytokine form, is a central pro-inflammatory signaling protein in the immune system. It is produced by multiple cell types, especially activated macrophages and T cells, and acts through TNF receptors to regulate inflammation, immune-cell activation, apoptosis, tissue remodeling, and host defense. Because of these broad effects, TNF is a major mediator in acute and chronic inflammatory disease and a frequent biomarker of inflammatory burden.

Biomedically, TNF is also a major therapeutic target. Excess TNF signaling is implicated in disorders such as rheumatoid arthritis, Crohn’s disease, diabetic complications, atherosclerosis, neuroinflammation, and tissue injury after ischemia or infection. Conversely, controlled TNF signaling can participate in regenerative or immune-reprogramming processes, as seen in recent studies of endometrial regeneration and immune microenvironment remodeling. This dual role makes TNF both a disease driver and a biologically important signaling node in tissue repair and immune regulation.

Focus of Latest Publications

Recent publications have examined TNF in a range of inflammatory and disease models, most often as a readout of immune activation or as a therapeutic target. In dogs with thoracolumbar intervertebral disc disease receiving acupuncture, plasma TNF-α was measured alongside neurological grading, HIF-1α, IL-6, and total plasma NAD(H). Neurological scores improved after treatment, and TNF-α showed significant treatment period-, disease phase-, and treatment method-dependent changes, with significant pre-post differences in the electroacupuncture group during both acute and preventive phases. These findings suggested that TNF-α may reflect phase- and method-dependent inflammatory responses after acupuncture, particularly with electroacupuncture.

TNF-α was also implicated in tissue regeneration and repair. In a mouse endometrial injury model integrated with human endometrial datasets, time-series single-cell and spatial omics showed that macrophages infiltrated early after injury and promoted the expansion and developmental reprogramming of SFRP4+ stromal cells during the regenerative phase. The study reported that macrophages promoted this reprogramming via TNF-α, and that TNF-α-induced SFRP4+ stromal cells enhanced regeneration after transplantation. In infected wound healing research, a biomineralized hydrogel incorporated TNF-α siRNA to silence TNF-α expression in macrophages, which reduced IL-6 and IL-1β, while also supporting antibacterial activity, angiogenesis, collagen deposition, and accelerated wound closure in mice.

Other studies evaluated TNF-α in neuroinflammation and drug discovery contexts. In a mouse model of polystyrene nanoplastic exposure, hippocampal damage and cognitive deficits were associated with oxidative stress, microglial activation, microglial extracellular trap formation, increased TNF-α and IL-1β, and neuronal ferroptosis; antioxidant treatment with N-acetylcysteine reduced these changes. In an Alzheimer's disease study, lawsone was assessed as a multitarget compound, and computational analyses showed binding affinity to TNF-α, while experimental work reported reduced proinflammatory markers including TNF-α together with improved cognitive and pathological outcomes. A separate in silico and in vitro study of a thiadiazole derivative identified notable affinity for the TNF binding site, with docking and molecular dynamics supporting a stable TNF-compound interaction, suggesting potential anticancer relevance.